Abstract
Background: Chronic lymphocytic leukaemia (CLL) cells are characterized by failures in the apoptosis pathway and increased proliferation, resulting in the progressive accumulation of B-lymphocytes in blood. Despite the wide range of antileukaemic drugs, CLL remains an incurable disease. However, a breakthrough is expected which will allow more effective treatment.
Objective: The study investigates the influence of poly(propyleneimine) (PPI) dendrimer with peripheral amino groups, 30% of which were coated with maltotriose (PPI-G4-OS-Mal-III), on CLL cells, and demonstrates that it acts through the induction of the apoptotic mechanism. It is important to note that the dendrimer was used as a drug itself and not as a drug carrier.
Method: CLL and normal lymphocytes were treated in vitro with the dendrimer, either alone or in combination with fludarabine (FA). The percentages of apoptotic and necrotic cells, and the protein expression, were checked using a flow cytometer. Gene expression was screened using a two-colour microarray with 60-mer probes.
Results: The results confirm that PPI-G4-OS-Mal-III influences the viability of CLL cells in vitro and does not exert any significant harmful effect on normal lymphocytes. The dendrimer appears to significantly influence gene and protein expression in CLL cells.
Conclusion: Since dendrimers can be specifically targeted, they may be very effective in CLL therapy, especially since in vitro PPI-G4-OS-Mal-III has been found to have stronger effect than fludarabine.
Keywords: Apoptosis, chronic lymphocytic leukaemia (CLL), dendrimers, gene expression, glycodendrimers, poly(propylene imine) (PPI), protein expression, toxicity.
Anti-Cancer Agents in Medicinal Chemistry
Title:Glycodendrimer PPI as a Potential Drug in Chronic Lymphocytic Leukaemia. The Influence of Glycodendrimer on Apoptosis in In Vitro B-CLL Cells Defined by Microarrays
Volume: 17 Issue: 1
Author(s): Ida Franiak-Pietryga, Ewelina Ziółkowska, Barbara Ziemba, Dietmar Appelhans, Henryk Maciejewski, Brigitte Voit, Aleksandra Kaczmarek, Tadeusz Robak, Barbara Klajnert-Maculewicz, Barbara Cebula-Obrzut, Piotr Smolewski, Maciej Borowiec and Maria Bryszewska
Affiliation:
Keywords: Apoptosis, chronic lymphocytic leukaemia (CLL), dendrimers, gene expression, glycodendrimers, poly(propylene imine) (PPI), protein expression, toxicity.
Abstract: Background: Chronic lymphocytic leukaemia (CLL) cells are characterized by failures in the apoptosis pathway and increased proliferation, resulting in the progressive accumulation of B-lymphocytes in blood. Despite the wide range of antileukaemic drugs, CLL remains an incurable disease. However, a breakthrough is expected which will allow more effective treatment.
Objective: The study investigates the influence of poly(propyleneimine) (PPI) dendrimer with peripheral amino groups, 30% of which were coated with maltotriose (PPI-G4-OS-Mal-III), on CLL cells, and demonstrates that it acts through the induction of the apoptotic mechanism. It is important to note that the dendrimer was used as a drug itself and not as a drug carrier.
Method: CLL and normal lymphocytes were treated in vitro with the dendrimer, either alone or in combination with fludarabine (FA). The percentages of apoptotic and necrotic cells, and the protein expression, were checked using a flow cytometer. Gene expression was screened using a two-colour microarray with 60-mer probes.
Results: The results confirm that PPI-G4-OS-Mal-III influences the viability of CLL cells in vitro and does not exert any significant harmful effect on normal lymphocytes. The dendrimer appears to significantly influence gene and protein expression in CLL cells.
Conclusion: Since dendrimers can be specifically targeted, they may be very effective in CLL therapy, especially since in vitro PPI-G4-OS-Mal-III has been found to have stronger effect than fludarabine.
Export Options
About this article
Cite this article as:
Franiak-Pietryga Ida, Ziółkowska Ewelina, Ziemba Barbara, Appelhans Dietmar, Maciejewski Henryk, Voit Brigitte, Kaczmarek Aleksandra, Robak Tadeusz, Klajnert-Maculewicz Barbara, Cebula-Obrzut Barbara, Smolewski Piotr, Borowiec Maciej and Bryszewska Maria, Glycodendrimer PPI as a Potential Drug in Chronic Lymphocytic Leukaemia. The Influence of Glycodendrimer on Apoptosis in In Vitro B-CLL Cells Defined by Microarrays, Anti-Cancer Agents in Medicinal Chemistry 2017; 17 (1) . https://dx.doi.org/10.2174/1871520616666160622092947
DOI https://dx.doi.org/10.2174/1871520616666160622092947 |
Print ISSN 1871-5206 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5992 |
Call for Papers in Thematic Issues
Induction of cell death in cancer cells by modulating telomerase activity using small molecule drugs
Telomeres are distinctive but short stretches present at the corners of chromosomes and aid in stabilizing chromosomal makeup. Resynthesis of telomeres supported by the activity of reverse transcriptase ribonucleoprotein complex telomerase. There is no any telomerase activity in human somatic cells, but the stem cells and germ cells undergone telomerase ...read more
Role of natural compounds as anti anti-cancer agents
Cancer is considered the leading cause of worldwide mortality, accounting for nearly 10 million deaths in 2022. Cancer outcome can be improved through an appropriate screening and early detection and through an efficient clinical treatment. Chemotherapy remains an important approach in treatment o f several types of cancers, even though ...read more
Signaling and enzymatic modulators in cancer treatment
Cancer accounts for nearly 10 million deaths in 2022 and is considered the leading cause of worldwide mortality. Cancer outcome can be improved through an appropriate screening and early detection and through an efficient clinical treatment. Chemotherapy, radiotherapy and surgery are the most important approach for the treatment of several ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
Related Articles
-
Antitumoral-Lipid-Based Nanoparticles: a Platform for Future Application in Osteosarcoma therapy
Current Pharmaceutical Design Topoisomerase I and II Inhibitors: A Patent Review
Recent Patents on Anti-Cancer Drug Discovery Drugs that Inhibit Tubulin Polymerization: The Particular Case of Podophyllotoxin and Analogues
Current Medicinal Chemistry - Anti-Cancer Agents CAR T-cell Therapy: A New Era in Cancer Immunotherapy
Current Pharmaceutical Biotechnology DNA Methyltransferase-1 Inhibitors as Epigenetic Therapy for Cancer
Current Cancer Drug Targets Extracellular Production of the Oncolytic Enzyme, L-Asparaginase, by Newly Isolated Streptomyces sp. Strain NEAE-95 as Potential Microbial Cell Factories: Optimization of Culture Conditions Using Response Surface Methodology
Current Pharmaceutical Biotechnology Impact of Splicing Factor Mutations on Pre-mRNA Splicing in the Myelodysplastic Syndromes
Current Pharmaceutical Design Expression of P-gp, MRP, LRP, GST-π and TopoIIα and Acquired Resistance to Cisplatin in Human Lung Adenocarcinoma Cells
Letters in Drug Design & Discovery Current Developments in the Therapeutic Potential of S-Nitrosoglutathione, an Endogenous NO-Donor Molecule
Current Pharmaceutical Biotechnology Exploring the Mitochondrial Apoptotic Cell Death Landscape and Associated Components Serving as Molecular Targets, Primarily for Synthetic and Natural Drugs Targeting Oncology Therapeutics
Current Molecular Pharmacology Network-Based Strategies Can Help Mono- and Poly-pharmacology Drug Discovery: A Systems Biology View
Current Pharmaceutical Design Patenting Human Genes and Stem Cells
Recent Patents on DNA & Gene Sequences Electrochemical Study of Ellipticine Interaction with Single and Double Stranded Oligonucleotides
Anti-Cancer Agents in Medicinal Chemistry Refractory Chronic Lymphocytic Leukemia: A Therapeutic Challenge
Current Cancer Drug Targets MicroRNAs in Tumorigenesis
Current Pharmaceutical Biotechnology Gene Therapy for Haemophagocytic Lymphohistiocytosis
Current Gene Therapy β-lactam Structured, 4-(4-(Methylsulfonyl)phenyl)-1-pentyl-3-phenoxyazetidin-2-one: Selectively Targets Cancerous B Lymphocyte Mitochondria
Anti-Cancer Agents in Medicinal Chemistry Myelodysplastic Syndromes: Review of Pathophysiology and Current Novel Treatment Approaches
Current Cancer Drug Targets Resistance in Cancer: A Target for Drug Discovery
Current Medicinal Chemistry - Anti-Cancer Agents The Role of Quercetin, Flavonols and Flavones in Modulating Inflammatory Cell Function
Inflammation & Allergy - Drug Targets (Discontinued)